Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats

Jane F. Reckelhoff, Bettye Sue Hennington, Vijaya Kanji, Lorraine C Racusen, Ann Marie Schmidt, Shi Du Yan, Jason Morrow, L. Jackson Roberts, Abdulla K. Salahudeen

Research output: Contribution to journalArticle

Abstract

We have previously shown that aging is associated with increased lipid peroxidation, reductions in renal function, and increased glomerular sclerosis. The mechanism(s) responsible for these age-related changes are not clear. The purpose of the present studies was to determine if there was an increase in inducible nitric oxide synthase (iNOS) with aging, and if so, whether inhibition of iNOS would prevent aging injury by preventing free radical-mediated lipid peroxidation, iNOS protein expression in the kidney increased by approximately 90% by 24 months. Inhibition of iNOS by aminoguanidine (0.1% in drinking water) for 9 months, beginning at 13 months of age, reduced blood pressure, improved glomerular filtration rate by 70%, and renal plasma flow by 40%, whereas glomerular sclerosis was considerably reduced. Renal F2-isoprostanes and malondialdehyde levels, markers of oxidative stress and lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine also did not attenuate immunostaining for advanced glycosylation end products (AGE) in the kidneys. These findings suggest that aminoguanidine attenuates aging renal dysfunction by inhibiting a pathophysiologic function of iNOS that is independent of free radical- mediated lipid peroxidation or significant effects on AGE deposition.

Original languageEnglish (US)
Pages (from-to)492-498
Number of pages7
JournalAmerican Journal of Hypertension
Volume12
Issue number5
DOIs
Publication statusPublished - May 1999

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Keywords

  • Advanced glycosylation end products
  • F2-isoprostanes
  • Free radicals
  • Glomerular filtration rate
  • Lipid peroxidation
  • Renal plasma flow

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reckelhoff, J. F., Hennington, B. S., Kanji, V., Racusen, L. C., Schmidt, A. M., Yan, S. D., ... Salahudeen, A. K. (1999). Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats. American Journal of Hypertension, 12(5), 492-498. https://doi.org/10.1016/S0895-7061(98)00264-7